ClinVar Miner

Submissions for variant NM_181882.2(PRX):c.2857C>T (p.Arg953Ter) (rs104894714)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201141 SCV000255810 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 4F 2014-11-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000236836 SCV000614803 pathogenic not provided 2014-11-18 criteria provided, single submitter clinical testing
Baylor Miraca Genetics Laboratories, RCV000201141 SCV000807618 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 4F 2017-09-01 criteria provided, single submitter clinical testing This variant has been previously reported as disease-causing and was found once in our laboratory homozygous in a 14-year-old female with Charcot Marie Tooth disease. Heterozygotes are expected to be asymptomatic carriers.
GeneDx RCV000236836 SCV000293535 pathogenic not provided 2018-12-06 criteria provided, single submitter clinical testing The R953X variant in the PRX gene has been reported previously in the compound heterozygous state in an individual with Dejerine-Sottas Neuropathy (Boerkoel et al., 2001). This variant is predicted to cause loss of normal protein function through protein truncation, as the last 509 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014). The R953X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R953X as a pathogenic variant.
Invitae RCV000458979 SCV000551417 pathogenic Charcot-Marie-Tooth disease type 4 2018-12-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the PRX mRNA at codon 953 (p.Arg953*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 509 amino acids (~35%) of the PRX protein. This variant is present in population databases (rs104894714, ExAC 0.02%). This variant has been reported in a family affected with Dejerine-Sottas syndrome (PMID: 11133365). A different truncation downstream of this variant (p.R1070*) has been determined to be pathogenic (PMID: 15197604, 22847150, 16770524). This suggests that deletion of this region of the PRX protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005053 SCV000025229 pathogenic Autosomal recessive Dejerine-Sottas syndrome 2001-02-01 no assertion criteria provided literature only

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